240 research outputs found

    Moxifloxacin: Clinically compatible contrast agent for multiphoton imaging

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    Multiphoton microscopy (MPM) is a nonlinear fluorescence microscopic technique widely used for cellular imaging of thick tissues and live animals in biological studies. However, MPM application to human tissues is limited by weak endogenous fluorescence in tissue and cytotoxicity of exogenous probes. Herein, we describe the applications of moxifloxacin, an FDA-approved antibiotic, as a cell-labeling agent for MPM. Moxifloxacin has bright intrinsic multiphoton fluorescence, good tissue penetration and high intracellular concentration. MPM with moxifloxacin was demonstrated in various cell lines, and animal tissues of cornea, skin, small intestine and bladder. Clinical application is promising since imaging based on moxifloxacin labeling could be 10 times faster than imaging based on endogenous fluorescence.1152sciescopu

    DMRN+17: Digital Music Research Network One-day Workshop 2022

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    DMRN+17: Digital Music Research Network One-day Workshop 2022 Queen Mary University of London - Tuesday 20th December 2022. The Digital Music Research Network (DMRN) aims to promote research in the area of Digital Music, by bringing together researchers from UK and overseas universities and industry for its annual workshop. The workshop will include invited and contributed talks and posters. The workshop will be an ideal opportunity for networking with other people working in the area. Keynote speakers: Sander Dieleman Tittle: On generative modelling and iterative refinement. Bio: Sander Dieleman is a Research Scientist at DeepMind in London, UK, where he has worked on the development of AlphaGo and WaveNet. He obtained his PhD from Ghent University in 2016, where he conducted research on feature learning and deep learning techniques for learning hierarchical representations of musical audio signals. His current research interests include representation learning and generative modelling of perceptual signals such as speech, music and visual data. DMRN+17 is sponsored by The UKRI Centre for Doctoral Training in Artificial Intelligence and Music (AIM); a leading PhD research programme aimed at the Music/Audio Technology and Creative Industries, based at Queen Mary University of London

    Large-Scale Pretrained Model for Self-Supervised Music Audio Representation Learning

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    Self-supervised learning technique is an under-explored topic for music audio due to the challenge of designing an appropriate training paradigm. We hence propose MAP-MERT, a large-scale music audio pre-trained model for general music understanding. We achieve performance that is comparable to the state-of-the-art pre-trained model Jukebox using less than 2% of parameters

    DMRN+16: Digital Music Research Network One-day Workshop 2021

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    DMRN+16: Digital Music Research Network One-day Workshop 2021 Queen Mary University of London Tuesday 21st December 2021 Keynote speakers Keynote 1. Prof. Sophie Scott -Director, Institute of Cognitive Neuroscience, UCL. Title: "Sound on the brain - insights from functional neuroimaging and neuroanatomy" Abstract In this talk I will use functional imaging and models of primate neuroanatomy to explore how sound is processed in the human brain. I will demonstrate that sound is represented cortically in different parallel streams. I will expand this to show how this can impact on the concept of auditory perception, which arguably incorporates multiple kinds of distinct perceptual processes. I will address the roles that subcortical processes play in this, and also the contributions from hemispheric asymmetries. Keynote 2: Prof. Gus Xia - Assistant Professor at NYU Shanghai Title: "Learning interpretable music representations: from human stupidity to artificial intelligence" Abstract Gus has been leading the Music X Lab in developing intelligent systems that help people better compose and learn music. In this talk, he will show us the importance of music representation for both humans and machines, and how to learn better music representations via the design of inductive bias. Once we got interpretable music representations, the potential applications are limitless

    DMRN+18: Digital Music Research Network One-day Workshop 2023

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    DMRN+18: Digital Music Research Network One-day Workshop 2023 Queen Mary University of London Tuesday 19th December 2023 • Keynote speaker: Stefan Bilbao The Digital Music Research Network (DMRN) aims to promote research in the area of digital music, by bringing together researchers from UK and overseas universities, as well as industry, for its annual workshop. The workshop will include invited and contributed talks and posters. The workshop will be an ideal opportunity for networking with other people working in the area. Keynote speakers: Stefan Bilbao Tittle: Physics-based Audio: Sound Synthesis and Virtual Acoustics. Abstract: Any acoustically-produced sound produced must be the result of physical laws that describe the dynamics of a given system---always at least partly mechanical, and sometimes with an electronic element as well. One approach to the synthesis of natural acoustic timbres, thus, is through simulation, often referred to in this context as physical modelling, or physics-based audio. In this talk, the principles of physics-based audio, and the various different approaches to simulation are described, followed by a set of examples covering: various musical instrument types; the important related problem of the emulation of room acoustics or “virtual acoustics”; the embedding of instruments in a 3D virtual space; electromechanical effects; and also new modular instrument designs based on physical laws, but without a counterpart in the real world. Some more technical details follow, including the strengths, weaknesses and limitations of such methods, and pointers to some links to data-centred black-box approaches to sound generation and effects processing. The talk concludes with some musical examples and recent work on moving such algorithms to a real-time setting.. Bio: Stefan is a Professor (full) at Reid School of Music, University of Edinburgh, he is the Personal Chair of Acoustics and Audio Signal Processing, Music. He currently works on computational acoustics, for applications in sound synthesis and virtual acoustics. Special topics of interest include: Finite difference time domain methods, distributed nonlinear systems such as strings and plates, architectural acoustics, spatial audio in simulation, multichannel sound synthesis, and hardware and software realizations. More information on: https://www.acoustics.ed.ac.uk/group-members/dr-stefan-bilbao/ DMRN+18 is sponsored by The UKRI Centre for Doctoral Training in Artificial Intelligence and Music (AIM); a leading PhD research programme aimed at the Music/Audio Technology and Creative Industries, based at Queen Mary University of London

    Effect of hypoxia and Beraprost sodium on human pulmonary arterial smooth muscle cell proliferation: the role of p27kip1

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    <p>Abstract</p> <p>Background</p> <p>Hypoxia induces the proliferation of pulmonary arterial smooth muscle cell (PASMC) <it>in vivo </it>and <it>in vitro</it>, and prostacyclin analogues are thought to inhibit the growth of PASMC. Previous studies suggest that p27<sup>kip1</sup>, a kind of cyclin-dependent kinase inhibitor, play an important role in the smooth muscle cell proliferation. However, the mechanism of hypoxia and the subcellular interactions between p27<sup>kip1 </sup>and prostacyclin analogues in human pulmonary arterial smooth muscle cell (HPASMC) are not fully understood.</p> <p>Methods</p> <p>We investigated the role of p27<sup>kip1 </sup>in the ability of Beraprost sodium (BPS; a stable prostacyclin analogue) to inhibit the proliferation of HPASMC during hypoxia. To clarify the biological effects of hypoxic air exposure and BPS on HPASMC, the cells were cultured in a hypoxic chamber under various oxygen concentrations (0.1–21%). Thereafter, DNA synthesis was measured as bromodeoxyuridine (BrdU) incorporation, the cell cycle was analyzed by flow cytometry with propidium iodide staining. The p27<sup>kip1 </sup>mRNA and protein expression and it's stability was measured by real-time RT-PCR and Western blotting. Further, we assessed the role of p27<sup>kip1 </sup>in HPASMC proliferation using p27<sup>kip1 </sup>gene knockdown using small interfering RNA (siRNA) transfection.</p> <p>Results</p> <p>Although severe hypoxia (0.1% oxygen) suppressed the proliferation of serum-stimulated HPASMC, moderate hypoxia (2% oxygen) enhanced proliferation in accordance with enhanced p27<sup>kip1 </sup>protein degradation, whereas BPS suppressed HPASMC proliferation under both hypoxic and normoxic conditions by suppressing p27<sup>kip1 </sup>degradation with intracellular cAMP-elevation. The 8-bromo-cyclic adenosine monophosphate (8-Br-cAMP), a cAMP analogue, had similar action as BPS in the regulation of p27<sup>kip1</sup>. Moderate hypoxia did not affect the stability of p27<sup>kip1 </sup>protein expression, but PDGF, known as major hypoxia-induced growth factors, significantly decreased p27<sup>kip1 </sup>protein stability. We also demonstrated that BPS and 8-Br-cAMP suppressed HPASMC proliferation under both hypoxic and normoxic conditions by blocking p27<sup>kip1 </sup>mRNA degradation. Furthermore, p27<sup>kip1 </sup>gene silencing partially attenuated the effects of BPS and partially restored hypoxia-induced proliferation.</p> <p>Conclusion</p> <p>Our study suggests that moderate hypoxia induces HPASMC proliferation, which is partially dependent of p27<sup>kip1 </sup>down-regulation probably <it>via </it>the induction of growth factors such as PDGF, and BPS inhibits both the cell proliferation and p27<sup>kip1 </sup>mRNA degradation through cAMP pathway.</p

    Women's Education Level, Maternal Health Facilities, Abortion Legislation and Maternal Deaths: A Natural Experiment in Chile from 1957 to 2007

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    The aim of this study was to assess the main factors related to maternal mortality reduction in large time series available in Chile in context of the United Nations' Millennium Development Goals (MDGs).Time series of maternal mortality ratio (MMR) from official data (National Institute of Statistics, 1957-2007) along with parallel time series of education years, income per capita, fertility rate (TFR), birth order, clean water, sanitary sewer, and delivery by skilled attendants were analysed using autoregressive models (ARIMA). Historical changes on the mortality trend including the effect of different educational and maternal health policies implemented in 1965, and legislation that prohibited abortion in 1989 were assessed utilizing segmented regression techniques.During the 50-year study period, the MMR decreased from 293.7 to 18.2/100,000 live births, a decrease of 93.8%. Women's education level modulated the effects of TFR, birth order, delivery by skilled attendants, clean water, and sanitary sewer access. In the fully adjusted model, for every additional year of maternal education there was a corresponding decrease in the MMR of 29.3/100,000 live births. A rapid phase of decline between 1965 and 1981 (-13.29/100,000 live births each year) and a slow phase between 1981 and 2007 (-1.59/100,000 live births each year) were identified. After abortion was prohibited, the MMR decreased from 41.3 to 12.7 per 100,000 live births (-69.2%). The slope of the MMR did not appear to be altered by the change in abortion law.Increasing education level appears to favourably impact the downward trend in the MMR, modulating other key factors such as access and utilization of maternal health facilities, changes in women's reproductive behaviour and improvements of the sanitary system. Consequently, different MDGs can act synergistically to improve maternal health. The reduction in the MMR is not related to the legal status of abortion

    The Butterfly Fauna Of The Italian Maritime Alps:Results Of The &#171;Edit&#187; Project

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    Bonelli, Simona, Barbero, Francesca, Casacci, Luca Pietro, Cerrato, Cristiana, Balletto, Emilio (2015): The butterfly fauna of the Italian Maritime Alps: results of the EDIT project. Zoosystema 37 (1): 139-167, DOI: 10.5252/z2015n1a6, URL: http://dx.doi.org/10.5252/z2015n1a

    Measurement of the prompt J/psi and psi(2S) polarizations in pp collisions at sqrt(s) = 7 TeV

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    The polarizations of prompt J/psi and psi(2S) mesons are measured in proton-proton collisions at sqrt(s) = 7 TeV, using a dimuon data sample collected by the CMS experiment at the LHC, corresponding to an integrated luminosity of 4.9 inverse femtobarns. The prompt J/psi and psi(2S) polarization parameters lambda[theta], lambda[phi], and lambda[theta, phi], as well as the frame-invariant quantity lambda(tilde), are measured from the dimuon decay angular distributions in three different polarization frames. The J/psi results are obtained in the transverse momentum range 14 &lt; pt &lt; 70 GeV, in the rapidity intervals abs(y) &lt; 0.6 and 0.6 &lt; abs(y) &lt; 1.2. The corresponding psi(2S) results cover 14 &lt; pt &lt; 50 GeV and include a third rapidity bin, 1.2 &lt; abs(y) &lt; 1.5. No evidence of large transverse or longitudinal polarizations is seen in these kinematic regions, which extend much beyond those previously explored

    The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

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    Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM (-/-) patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors
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